Quality assurance, quality control and accreditation.
Explore the source record for details and available documents.
Accreditation↗
Biomedical subjects
G G de Lange
Publications and source records attributed to G G de Lange.
Evaluation of monoclonal antibodies with specificity for human IgA, IgA subclasses and allotypes and secretory component. Results of an IUIS/WHO collaborative study.
51 monoclonal antibodies (McAb) with putative specificity for human IgA, the IgA subclasses, Am allotypes or secretory component (SC) were evaluated for immunoreactivity and specificity by nine laboratories employing immunodiffusion, agglutination, immunohistological assays, immunoblotting and direct binding and competitive inhibition enzyme immunoassays. McAbs specific for IgA PAN (n = 24), IgA1 (n = 7), IgA2 (n = 3), IgA2m(2) (n = 2), non-IgA2m(2) (n = 4) and SC or secretory IgA (n = 5) were identified that were immunoreactive and specific in the assays employed. The McAbs identified as IgA- or SC-reactive were shown to be non-reactive to human IgG, IgM, IgD, IgE, kappa and lambda by direct binding and competitive inhibition immunoassays. Interestingly, no McAbs with restricted specificity for IgA2m(1) were identified. Some McAbs displayed higher affinity and/or better performance in one or several of the assay groups. The IgA- and SC-specific McAbs identified in this international collaborative study have potential as immunochemical reference reagents to identify and quantitate monomeric and polymeric IgA in human serum and secretions.
Animals↗
The origin of IgG production and homogeneous IgG components after allogeneic bone marrow transplantation.
Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma.
Anemia, Aplastic↗
Molecular characterization of Gm(n+) and G2m(n-) allotypes.
Immunoglobulin (Ig) allotype typing is usually performed with serological methods based on hemagglutination inhibition. The recent development of molecular techniques has allowed the molecular typing of several Ig markers. The hinge, CH2, and CH3 domains of the G2 gene from six unrelated individuals (three G2m(n+) and three G2m(n-)) were amplified and cloned to establish the molecular basis of the G2mn+ and G2mn- . Comparison of the allele sequences revealed three changes: two (codons 308 and 437) are silent exonic substitutions, one is a G to A transition corresponding to an amino acid difference in position 282: Val (GTG) in G2mn- , Met (ATG) in G2mn+ . These substitutions were identified via two approaches: 282 polymorphism, after digestion of a specific polymerase chain reaction product with Nla III followed by acrylamide electrophoresis; 308 and 437, by a dot-blot technique using allele-specific oligonucleotides. These molecular typing results correspond exactly to those obtained serologically; moreover, the three substitutions defining the G2mn+ and G2mn- alleles are always associated in a strict linkage disequilibrium.
Base Sequence↗
DNA sequences specific for Caucasian G3m(b) and (g) allotypes: allotyping at the genomic level.
Assignment of the G3m(g) and (b) correlative amino acid residues was performed at the genomic level by direct sequencing of DNA from nine Caucasian individuals. Two oligonucleotide primers were used for subclass-specific enzymatic amplification of a DNA segment comprising a major portion of the second and third constant region domains (CH2 and CH3) of the human IgG3 heavy chain gene. Comparison of the sequences of amplified DNA from individuals serologically typed as homozygous for G3m(b) or G3m(g) or as heterozygous, G3m(b,g), revealed differences in the codons for the amino acid residues 291, 296, and 384. Proline, phenylalanine, and serine at these positions corresponded to G3m(b), and leucine, tyrosine, and asparagine to G3m(g). Heterozygotic individuals, typed G3m(b,g), displayed both the G3m(b) and G3m(g) codons at these three positions. The polymorphism at each of these three codons could be identified either as the appearance, or the loss, of recognition sites for the two restriction endonucleases, Nsp BII and Rsa I. This allowed the development of a polymerase chain reaction (PCR)-based assay permitting the distinction of G3mb and G3mg alleles by analyzing the electrophoretical mobility of the DNA fragments generated by digestion of the PCR-products with Nsp BII and Rsa I.
Amino Acid Sequence↗
Evaluation of monoclonal antibodies having specificity for human IgG subclasses: results of the 2nd IUIS/WHO collaborative study.
Following the 1st IUIS/WHO Collaborative Study of monoclonal anti-IgG subclass antibodies, a panel of WHO Specificity Reference Reagents (SRR) was established [Jefferis, R., et al. (1985) Immunol. Lett., 10, 223]. At the time, the hope was expressed that further reagents particularly for IgG2, and other allotypic specificities would become available which could be applied in a wide range of assay protocols. The 2nd study reports the evaluation of nineteen anti-subclass and seven anti-allotype monoclonal antibodies. The anti-IgG1 antibody HP6187 was equivalent in performance to the SRR. Others, that were not of the mouse IgG1 isotype, may be useful for particular applications. The anti-IgG2 antibody HP6200 could be a valuable addition to the WHO SRR; it is specific for an epitope in the Fab region but does not have the light chain bias of HP6014. Antibodies of putative allotype specificity exhibited the claimed specificity when used within protocols similar to those employed by the originating laboratory. It appears to be inherent in the nature of the epitopes (allotopes) recognized that it will take several years before reagents applicable to a wide range of techniques will become available.
Antibodies, Anti-Idiotypic↗
Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: evidence for donor origin of the antibody producing cells.
A rapid recovery of specific humoral immunity in the recipient of an allogeneic bone marrow transplantation (BMT) can be observed after immunization of the donor before graft sampling. This has been attributed to transfer of specific immunity from donor to recipient. However, to maintain the concept of transfer the origin of the antibody producing cells in the recipient after BMT must be demonstrated. To this end, donor-recipient pairs with differences in Gm-allotypes were selected and immunized before BMT with the neo-antigen Helix pomatia haemocyanin (HPH) according to three immunization protocols. Additionally, the recipients were immunized at day 42 after BMT. Serum samples were weekly obtained from the recipients in the first 100 d after BMT. The origin of HPH-specific antibody producing cells was assessed by two approaches: (1) determination of the Gm-allotypes of anti-HPH antibodies within a distinct IgG subclass, (2) analysis of anti-HPH antibody spectrotypes by isoelectric focusing combined with immunoblotting. The results obtained with these two approaches show concordance in most instances and led to the conclusion that the antibody producing cells are of donor origin.
Adult↗
Immunoglobulin allotypes are not associated with HLA-antigens, autoantibodies and clinical symptoms in systemic lupus erythematosus. Members of the SLE Study Group.
Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.
Autoantibodies↗
Allotypes and other epitopes of immunoglobulins.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Immunoglobulin allotypes in systemic lupus erythematosus--results of a central European multicenter study. SLE Study Group.
Immunoglobulin heavy chains (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies were examined in 323 central European Caucasian patients with systemic lupus erythematosus (SLE). No significant differences were found between the different allotype or phenotype frequencies of the SLE patients and a control group of healthy individuals. Our results indicate that Gm, A2m and Km allotypes do not represent susceptibility factors for SLE in Caucasians.
Gene Frequency↗
Attempt to calculate the allele frequency distribution of a TaqI RFLP detected by the highly polymorphic probe YNH24.
To improve the analysis of parentage testing with the additional technique of DNA polymorphisms, the usefulness of probe YNH24 was studied. The allele frequency distribution of restriction fragments detected by probe YNH24 on TaqI-digested genomic DNA from 100 unrelated individuals was determined. For this purpose, the size of the fragments was calculated by making use of HindIII-digested lambda DNA as an internal marker and of a digitizing tablet coupled to a computer. The size of the fragments ranged from 2.53 kb to 5.89 kb. The mean standard deviation was 0.05 kb. The differences between the fragment sizes appeared to be smaller than the standard deviation. For this reason, it was not possible to calculate the allele frequency distribution of this highly polymorphic genetic system.
Alleles↗
Multiple levels of analysis of an IGHG4 gene deletion.
Human immunoglobulin heavy chain constant region (IGHC) genes constitute a typical multigene family, usually comprising eleven genes on the telomere of chromosome 14 (14q32). In this region, deleted and duplicated haplotypes have been reported to exist with considerable frequency. Their origin is the result of either unequal crossing-over or looping out excision. In this paper, we report the characterization of a new type of deletion, involving the IGHG4 gene, in a subject who also carries a larger deletion of a previously described type on the second chromosome. Employment of several methods (polymerase chain reaction, standard Southern blot, pulsed field gel electrophoresis, serological techniques) to analyze these deleted haplotypes has resulted in a level of accuracy in their characterization that has not been achieved in previous cases. The site of recombination responsible for the IGHG4 deletion was restricted to a 2.5-kb region 3' of the G4 gene; this rules out any possible involvement of the S regions in the recombination process. The usefulness of the various techniques in the characterization of the deletions is also discussed, together with possible future applications in the field.
Base Sequence↗
Evaluation of monoclonal antibodies with putative specificity for human IgG allotypes.
Fourteen monoclonal antibodies (MAbs) of putative specificity for human IgG allotypes and isoallotypes were evaluated for reactivity and specificity in 8 different assay systems. The study showed that the MAbs tested could be classified into 1 of 4 groups: those exhibiting allotypic specificity regardless of the assay system, allotypic specificity dependent on the assay system, isoallotypic specificity, and those showing neither allotypic nor isoallotypic specificity. These observations were presumably dependent on antigen presentation, epitope integrity and/or antibody multispecificity. For the G1m(a), G1m(f), G1m(z), G3m(g) and G3m(u) specificities, MAbs have been produced which can be used for routine typing purposes in defined haemagglutination and enzyme-linked immunosorbent assay systems. MAbs are also available that show 'non-g' isoallotypic specificity.
Animals↗
A sandwich ELISA with monoclonal anti-IgG allotype antibodies permitting the deduction of the G1m genotype.
With murine monoclonal antibodies specific for the human IgG1 allotypes G1m(z), G1m(a), G1m(f) and the IgG1 subclass, sandwich enzyme-linked immunosorbent assays (ELISAs) were developed to determine whether different allotypic determinants are located on the same molecule. With the conventional haemagglutination-inhibition test, it is only possible to determine the phenotype. With this ELISA system, it is now possible to deduce the G1m genotype.
Alleles↗
Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions.
Selective IgG1 deficiency is a rare disease. We report a familial form of IgG1 deficiency, in which IgG1 was undetectable in a 5-yr-old girl with a history of asthma and respiratory tract infections. Her father had an IgG1 level that was one-third of the mean amount found in normal healthy controls. The defect in the proband was caused by a homozygous deletion of the structural gene for C gamma 1. A Southern blot analysis demonstrated that the maternal haplotype contained a deletion encompassing C gamma 1, C psi epsilon 1, C alpha 1, C psi gamma, and C gamma 2, whereas the deletion on the paternal haplotype was confined to the C gamma 1 gene. Neither of these deletions has previously been reported. IgG1 normally constitutes the dominant isotype for antibodies directed against protein Ag, including viral proteins. We have analyzed the immune response to a number of different protein and polysaccharide Ag in the patient and her parents. In the proband, antiviral antibodies were restricted to the IgG3 and IgG4 subclasses. However, the total amount of IgG directed against several viruses was below the concentration found in normal seropositive individuals. The father and the paternal grandfather, both with low serum IgG1 levels, also had asthma, thus indicating a possible causal relationship.
Adult↗
Polyclonal hyper-immunoglobulin G1(A1) syndrome. Evidence for a dominant immunoglobulin production regulator within the human immunoglobulin heavy chain gene complex.
The hyper-IgG1(A1) syndrome entails a polyclonal selective increase of the serum levels of immunoglobulin (Ig) G1 and to a lesser extent of IgA1; this is not mediated by malignancy, infectious or autoimmune diseases or environmental agents. In three generations of a family, all the affected individuals carried an immunoglobulin heavy chain (IgH) allele distinguished by restriction fragment length polymorphism analysis; the IgH allele was not present in non-affected family members. A 32:1 chance for the linkage of this rare IgH haplotype with the hyper-IgG1(A1) syndrome in the family argues for a dominant regulator located at the human IgH locus having a selective influence on the production of IgG1 and IgA1.
Female↗
Inheritance of a large deletion within the human immunoglobulin heavy chain constant region gene complex and immunological implications.
A deletion of the immunoglobulin heavy chain (IgH) pseudo-gamma, gamma-2, gamma-4, epsilon, and alpha-2 constant region gene segments was found to segregate unchanged in three generations of a family. The IgG1 locus on the IgH allele carrying the deletion was expressed to the same extent as its normal counterpart. One individual who was heterozygous for the deletion had an IgG2 deficiency, whereas the four other heterozygous individuals had serum levels of IgG2 and IgG4 within the normal ranges. IgA2 levels were low or below the normal range in all heterozygous individuals. The data indicate that the expression of some Ig isotypes can be decreased by hemizygous deletions, possibly due to a lower probability for switching.
Alleles↗
Characterization of an IgG2, G2m(23) anti-Rh-D antibody.
IgG2, G2m(23) anti-Rh-D antibodies were detected in the serum of a donor. It has been characterized by Gm typing and the use of polyclonal and mouse monoclonal anti-IgG subclasses (which had proved to be satisfactory for agglutination of sensitized red blood cells). This anti-D constitutes a good reagent for G2m(23) typing.
Antibodies, Monoclonal↗